R5-delta32, CCR2-V64I and a third gene.<P/ These have been identified by pursuing an approach of examining over 170 candidate genes in patient cohorts for testing hypotheses of susceptibility to HIV-1 and progression to AIDS. For the longer term, we have been developing a novel method for disease gene identification in patient cohorts called "Mapping by Admixture Linkage Disequilibrium" (MALD; See Project #Z01 BC 10261-01 LGD). Candidate gene screening of polymorphisms in or near a gene depends on fine scale linkage disequilbrium that exists in human populations. Screening with the candidate genes that currently have known polymorphisms and additional loci that become available is ongoing through the identification of polymorphisms for the remaining loci. In this work, single strand conformation polymorphism /heteroduplex analysis and polymorphisms from the literature are followed by sequence analysis and conversion of these polymorphisms to PCR formatted assays. Several thousand DNAs of HIV-exposed and -infected individuals have been organized and aliquoted into 96-well format PCR plates for accurate and reliable high-throughput genotyping of the 37-plate Mega panel. Genotyping allows performance of survival and categorical analysis to determine relationships between genotypes and phenotypes making possible estimates of the relative risks and hazards of genetic polymorphisms that influence HIV-1 infection and disease progression. " The aim of this project is to identify novel host genes and polymorphisms involved in HIV-1 infection and progression to AIDS through an examination of candidate genes along with a mapping by admixture linkage disequilibrium (MALD) genome scan. The Laboratory of Genomic Diversity (LGD) has samples from almost 4,000 individuals with a history of HIV-1 exposure or infection. A high-throughput, polymerase chain reaction (PCR)-based genotyping laboratory that has assayed numerous candidate gene polymorphisms in thousands of HIV-infected and - exposed patients has been developed.